Can the immersion time of PUVA bath therapy be shortened?
Up to now, there are only a few data available concerning the influence of bathing time on skin phototoxicity. We compared the erythemal responses of normal skin to bath PUVA with 8-methoxypsoralen (8-MOP) after 5, 10 and 20 min immersion time. Currently, 20 min is the routinely performed immersion time in many European countries, including Germany, while in other countries bathing times are shorter. The minimal phototoxic dose (MPD) following immersion times of 5 min and 10 min in a warm water bath (37 degrees C) containing 1 mg/l 8-MOP was compared to the MPD following 20 min immersion time in a half-sided manner in a total of 24 patients. Our results revealed that an immersion time of 5 min did not yield a detectable erythema after 72 h. In contrast, both 10 and 20 min PUVA baths induced visible erythemas with a significantly higher median MPD following 10 min immersion (2.25 J/cm2) compared to 20 min baths (1.5 J/cm2). As an erythemal response of 8-MOP PUVA bath seems reduced after shorter immersion times, comparative studies on the clinical efficacy using shorter time regimens have to be conducted before conclusive recommendations for clinical PUVA-bathing time can be given.


Surgical bleeding in microgravity.
A surgical procedure performed during space flight would occur in a unique microgravity environment. Several experiments performed during weightlessness in parabolic flight were reviewed to ascertain the behavior of surgical bleeding in microgravity. Simulations of bleeding using dyed fluid and citrated bovine blood, as well as actual arterial and venous bleeding in rabbits, were examined. The high surface tension property of blood promotes the formation of large fluid domes, which have a tendency to adhere to the wound. The use of sponges and suction will be adequate to prevent cabin atmosphere contamination with all bleeding, with the exception of temporary arterial droplet streams. The control of the bleeding with standard surgical techniques should not be difficult.


PGL4 syndrome in a patient with synchronous paraganglioma-pheochromocytoma.
Pheochromocytoma and paraganglioma (PGL) are rare neuroendocrine tumours, frequently associated with genetic syndromes. We report the case of a man in his 40s with a left anterior neck mass and a history of hypertensive crisis, heavy sweating and constipation. Biochemical tests showed increased plasma and urine normetanephrines. Neck ultrasound suggested left carotid body PGL, but it was mandatory to search for other lesions. Whole-body MIBG failed to show abnormal uptake. Abdominal MRI was suggestive of another PGL, anterior to the right adrenal gland. Abdominal surgery was performed uneventfully under alpha and beta blockers. This intervention proved to be effective, as normetanephrines levels became completely normal after 1 month. Carotid body PGL was successfully excised 4-months later. Genetic study identified a large deletion in exon 1 of the SDHB gene allowing the diagnosis of paraganglioma syndrome type 4 (PGL4). After 19 months of follow-up, he is still on clinical and biochemical remission and will continue life-long surveillance.


Systematic Therapeutic Drug Monitoring for Linezolid: Variability and Clinical Impact.
Linezolid serum trough (Cmin) and peak (Cmax) levels were determined prospectively in 90 patients. Adequate exposure was defined as a Cmin of 2 to 8 mg/liter. Therapy was empirical (73.3%) or targeted (26.7%). Wide interindividual variability in linezolid Cmin levels was recorded (0.1 to 25.2 μg/ml). Overall, 65.5% of the patients had out-of-range, 41.1% had subtherapeutic, and 24.4% had supratherapeutic trough levels. We did not find a correlation between abnormal levels and adverse events, in-hospital mortality, or overall poor outcome.


Hormonal and electrolyte responses of conscious sheep to 96 h of hypoxia.
Hypoxia alters the relationship of aldosterone secretion to plasma renin activity. The potential role plasma electrolytes play in this modification is not clear. This study analyzed the interrelationships among renin, aldosterone, vasopressin (ADH), and plasma electrolytes during 96 h of normobaric hypoxia. Eight ewes were exposed, in discrete experiments, to hypocapnic hypoxia [arterial O2 tension (PaO2) 37-42 mmHg, arterial CO2 tension (PaCO2) 26-28 mmHg] and eucapnic hypoxia (PaO2 40-43 mmHg, PaCO2 28-31 mmHg) by N2 dilution in an environmental chamber. Urine output (24 h) was measured, and arterial plasma samples were collected during the normoxic control period and at 24-h intervals of hypoxia. Plasma Na+, K+, renin, and ADH levels did not change from the normoxic values during either hypocapnic or eucapnic hypoxia. However, urinary aldosterone excretion [critical significance (alpha) less than 0.046] and K+ excretion (alpha less than 0.046) decreased markedly during each type of hypoxia. All sheep developed a pronounced negative K+ balance by 96 h of hypoxia. These data suggest that plasma K+ concentration is preserved by movement of K+ out of the intracellular compartment; this change in K+ distribution may inhibit aldosterone secretion during hypoxia.


An established human cell line derived from a malignant mediastinal teratoma.
An established cell line derived from a human malignant mediastinal teratoma is described. The cell line was composed of slightly atypical fibroblast cells with a population-doubling time of 24 h at the exponential growth phase. The reason why the emerging cell line became fibroblastic although other tissues were present in the original tumor may be that fibroblasts so readily grow in culture. Chromosome banding showed a hypertriploid stemline number, S = 78. Almost all of the analysed karyotypes had seven markers in common. Eleven other markers, occurring at low frequency, were also detected. The origin of all markers except one could be deduced.


Constitutive association of BRCA1 and c-Abl and its ATM-dependent disruption after irradiation.
BRCA1 plays an important role in mechanisms of response to double-strand breaks, participating in genome surveillance, DNA repair, and cell cycle checkpoint arrests. Here, we identify a constitutive BRCA1-c-Abl complex and provide evidence for a direct interaction between the PXXP motif in the C terminus of BRCA1 and the SH3 domain of c-Abl. Following exposure to ionizing radiation (IR), the BRCA1-c-Abl complex is disrupted in an ATM-dependent manner, which correlates temporally with ATM-dependent phosphorylation of BRCA1 and ATM-dependent enhancement of the tyrosine kinase activity of c-Abl. The BRCA1-c-Abl interaction is affected by radiation-induced modification to both BRCA1 and c-Abl. We show that the C terminus of BRCA1 is phosphorylated by c-Abl in vitro. In vivo, BRCA1 is phosphorylated at tyrosine residues in an ATM-dependent, radiation-dependent manner. Tyrosine phosphorylation of BRCA1, however, is not required for the disruption of the BRCA1-c-Abl complex. BRCA1-mutated cells exhibit constitutively high c-Abl kinase activity that is not further increased on exposure to IR. We suggest a model in which BRCA1 acts in concert with ATM to regulate c-Abl tyrosine kinase activity.


The impact of resuscitated fecal peritonitis on the expression of the hepatic bile salt transporters in a porcine model.
Sepsis is often associated with cholestatic liver dysfunction caused by changes in the expression profile of hepatic bile salt transporters. However, in rodent endotoxin models, the role of ischemic hepatitis caused by liver hypoperfusion cannot be delineated. We hypothesized that hepatocytes change their expression pattern of bile salt transporters during early severe sepsis despite adequate resuscitation. Fifteen anesthetized and instrumented pigs were randomized to either fecal peritonitis (n = 8) or control (n = 7). Resuscitation was performed by hydroxyethyl starch and norepinephrine infusion. Hemodynamic parameters and markers of cholestatic and ischemic hepatic dysfunction were recorded. At baseline and after 21 h, messenger RNA (mRNA) and protein expression of bile salt transporters was determined by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively, on in vivo liver biopsies. All resuscitated septic pigs developed a normotensive hyperdynamic circulation with increased portal flow. After 21 h of peritonitis, no signs of biochemical or histological cholestasis were present. Na-taurocholate cotransporting polypeptide and bile salt export pump mRNA were downregulated by 83% (P = 0.001) and 67% (P = 0.001), respectively, in comparison with controls, whereas multidrug resistance-associated protein 4 (MRP4) mRNA was upregulated by 85% (P = 0.02). Bile salt export pump and MRP2 staining were downregulated in septic pigs. During early porcine fluid-resuscitated sepsis, hepatic basolateral influx (Na-taurocholate cotransporting polypeptide) and canalicular efflux (bile salt export pump) of bile salts were downregulated without hemodynamic signs of hepatic hypoperfusion or biochemical signs of cholestasis. In parallel, the basolateral escape transport (MRP4) was markedly upregulated, possibly as an early adaptive response to counteract hepatocellular accumulation of toxic bile acids.


Health and Health Needs of Children of Women Seeking Services for and Safety From Intimate Partner Violence.
Children exposed to intimate partner violence (IPV) are at increased risk for health problems. The moment that a mother seeks services for or safety from IPV may be a window of opportunity to offer needed health care for her children. The objective of the study is to describe the perceptions of child health conditions and needs among mothers seeking services for or safety from IPV, and to compare the results in shelter- versus community-based samples. A cross-sectional survey of women with at least one child of age 3 to 11 years seeking services at an urban YWCA, which supports a residential IPV shelter and a community-based family justice center, was done between fall 2013 and winter 2014. Child health conditions were captured using the Children With Special Health Care Needs survey and the Strengths and Difficulties Questionnaire. Prevalence of health conditions among IPV-exposed children was compared with population norms. Perceived child health and health needs in the residential versus community settings were compared. Women (n = 48) completed surveys related to 91 children. Special health care needs (25%) and behavioral health (52%) problems were significantly higher in our sample than in general populations. Almost one quarter (24%) of children had a current need for general medical care and almost one half (44%) had a current need for behavioral health care. No significant differences in child health conditions or needs between residential and community settings were observed. These findings extend prior research describing the health problems faced by children exposed to IPV by describing maternal perceptions of child health and need for health care in a critical moment of seeking help for IPV. Community agencies may use this window of opportunity to support child health and household safety.


Artisanal Extraction and Traditional Knowledge Associated with Medicinal Use of Crabwood Oil (Carapa guianensis Aublet.) in a Peri-Urban Várzea Environment in the Amazon Estuary.
Várzea forests of the Amazon estuary contain species of importance to riverine communities. For example, the oil extracted from the seeds of crabwood trees is traditionally used to combat various illnesses and as such artisanal extraction processes have been maintained. The objectives of this study were to (1) describe the process involved in artisanal extraction of crabwood oil in the Fazendinha Protected Area, in the state of Amapá; (2) characterise the processes of knowledge transfer associated with the extraction and use of crabwood oil within a peri-urban riverine community; and (3) discern medicinal uses of the oil. The data were obtained using semistructured interviews with 13 community members involved in crabwood oil extraction and via direct observation. The process of oil extraction is divided into four stages: seed collection; cooking and resting of the seeds; shelling of the seeds and dough preparation; and oil collection. Oil extraction is carried out within the home for personal use, with surplus marketed within the community. More than 90% of the members of the community involved in extraction of crabwood oil highlighted the use of the oil to combat inflammation of the throat. Knowledge transfer occurs via oral transmission and through direct observation.


Nausea and vomiting of pregnancy in an evolutionary perspective.
The proximate mechanisms underlying gestational nausea and vomiting have been intensively studied, but the possibility that the symptoms themselves serve a useful function has only recently been considered seriously. We synthesized evidence to evaluate various hypotheses for the adaptive significance of nausea and vomiting of pregnancy, as well as the possibility that symptoms are nonfunctional byproducts of pregnancy hormones. We found greatest support for the hypothesis that normal levels of nausea and vomiting of pregnancy (excluding hyperemesis) protect pregnant women and their embryos from harmful substances in food, particularly pathogenic microorganisms in meat products and toxins in strong-tasting plants. We discuss the data that support critical predictions of this "maternal and embryo protection hypothesis" (and contradict other hypotheses), as well as appropriate implications of these results. Knowledge that normal nausea and vomiting of pregnancy indicates the functioning of a woman's defense system, rather than a bodily malfunction, may reassure patients and enable health care providers to develop new ways of minimizing the uncomfortable symptoms.


Effect of probiotic strains on interleukin 8 production by HT29/19A cells.
Promising results from clinical studies on the effect of probiotics as maintenance therapy in inflammatory bowel disease and in the prevention of onset of pouchitis ask for studies to unravel the still poorly understood mechanism of action of probiotics. To evaluate whether the probiotic bacteria that were used in the clinical studies (VSL#3, Escherichia coli Nissle 1917, and Lactobacillus GG) are able to induce chemokine production in epithelial cells, HT29/19A monolayers were incubated with cell debris and cell extract fractions of single strains of the probiotic bacteria in doses ranging from 10(3) to 10(9) colony-forming units/ml for 32 h. Supernatants were measured for interleukin 8 by ELISA. Lactobacilli and bifidobacteria strains from VSL#3 and Lactobacillus GG did not induce interleukin 8, whereas both cell debris and cell extracts from E. coli Nissle 1917 induced interleukin 8 production in a dose-dependent way. Cell extracts from streptococcal strains induced interleukin 8 when applied at high concentrations. Probiotic Gram-positive bacteria did not induce interleukin 8, whereas the nonpathogenic, Gram-negative E. coli Nissle 1917 strain induced interleukin 8 in a dose-dependent way in this culture model. These results suggest that probiotic Gram-positive bacteria and E. coli Nissle 1917 may exert their beneficial effects on the host by a different mechanism of action.


Role of immunologic mechanisms in tubulointerstitial nephropathies.
The immunologic basis of various glomerulonephropathies has been widely investigated and highly publicized. Little recognition, however, has been given to the possible role of the immune system in the genesis of tubulointerstitial nephropathies. Considerable clinical and experimental data have recently appeared suggesting the possible role of immunologic mechanisms in the genesis of various tubulointerstitial nephropathies. This article is intended to review the available clinical and experimental data pertaining to this issue.


Portal vein pulsatility and spectral width changes in patients with portal hypertension: relation to the severity of liver disease.
Using Doppler ultrasound in patients with chronic liver disease (CLD) and portal hypertension, portal vein pulsatility pattern and spectral width changes were assessed and evaluated in relation to the severity of liver disease as determined according to the Child-Pugh score. The pulsatility index (PI) was significantly lower in CLD patients (mean+/-SD: 0.23+/-0.08) compared with healthy subjects (0.39+/-0.1) (p<0.001) and lower in Child-Pugh class C compared with Child-Pugh class A patients (0.21+/-0.07 vs 0.25+/-0.08, respectively) (p<0.05). The spectral width index was significantly higher in CLD patients vs healthy subjects (0.91+/-0.16 vs 0.60+/-0.12, respectively) (p<0.001). The difference was also noted in the early stage (Child-Pugh A patients) when compared with healthy subjects (0.88+/-0.17). In conclusion, portal vein pulsatility and spectral width indices can reflect the early haemodynamic changes in CLD patients. These changes become more pronounced with the progression of liver disease.


Superiority of ABTS over Trinder reagent as chromogen in highly sensitive peroxidase assays for enzyme linked immunoadsorbent assay.
Most of the currently used enzyme immunological assays employ horse radish peroxidase as marker enzyme. A comparison is presented of ABTS (2,2'-azino-di-(3-ethyl benzthiazoline-6-sulphonic acid) and the Trinder reagent as chromogens for the detection of small amounts of solid-phase peroxidase. The formation of chromophore using the Trinder reagent under the conditions described by Gallati (J. Clin. Chem. Clin. Biochem. (1977) 15, 699-703) reaches a plateau after 3-4 h due to H2O2 induced inactivation of the enzyme. In contrast, with suitable temperature and concentrations of H2O2 and ABTS, chromophore production continues in this system for at least 20 h. In an Enzyme Linked Immunoadsorbent Assay for antibodies to myelin basic protein the use of the ABTS/H2O2 substrate system described here gives an assay 14 times more sensitive than the maximum possible with Trinder reagent.


Dependence of quasiliquid thickness on the liquid activity: a bulk thermodynamic theory of the interface.
Studies of the phenomenon of quasiliquid formation span systems as diverse as noble gases, complex organic molecules, and metals, and span triple point temperatures from 25 to 933 K. We show that when viewed as a single phenomenon essentially all published measurements of the quasiliquid layer thickness on solids below the melting point can be plotted as a function of the thermodynamic activity. Two classes of behavior are then observed: one for molecular systems and one for atomic systems. We derive a dependence on activity through a grand canonical lattice gas calculation. This is the only such unifying theory of this phenomenon.


Genomic Correlates of Disease Progression and Treatment Response in Prospectively Characterized Gliomas.
The genomic landscape of gliomas has been characterized and now contributes to disease classification, yet the relationship between molecular profile and disease progression and treatment response remain poorly understood.Experimental Design: We integrated prospective clinical sequencing of 1,004 primary and recurrent tumors from 923 glioma patients with clinical and treatment phenotypes. Thirteen percent of glioma patients harbored a pathogenic germline variant, including a subset associated with heritable genetic syndromes and variants mediating DNA repair dysfunctions (29% of the total) that were associated with somatic biallelic inactivation and mechanism-specific somatic phenotypes. In astrocytomas, genomic alterations in effectors of cell-cycle progression correlated with aggressive disease independent of IDH mutation status, arose preferentially in enhancing tumors (44% vs. 8%, P < 0.001), were associated with rapid disease progression following tumor recurrence (HR = 2.6, P = 0.02), and likely preceded the acquisition of alkylating therapy-associated somatic hypermutation. Thirty-two percent of patients harbored a potentially therapeutically actionable lesion, of whom 11% received targeted therapies. In BRAF-mutant gliomas, response to agents targeting the RAF/MEK/ERK signaling axis was influenced by the type of mutation, its clonality, and its cellular and genomic context. These data reveal genomic correlates of disease progression and treatment response in diverse types of glioma and highlight the potential utility of incorporating genomic information into the clinical decision-making for patients with glioma.


History Leaves Its Mark on Soil Bacterial Diversity.
Dispersal is closely tied to the origin and maintenance of microbial diversity. With its focus on a narrow group of soil bacteria, recent work by Andam and colleagues on Streptomyces has provided perhaps the strongest support so far that some bacterial diversity in soils can be attributed to regional endemism (C. P. Andam et al., mBio 7:e02200-15, 2016, http://dx.doi.org/10.1128/mBio.02200-15). This means that dispersal is limited enough to allow for evolutionary diversification. Further analyses suggest that signatures of climate conditions more than 10,000 years ago can be detected in contemporary populations of this genus. These legacies have implications for how future climate change might alter soil microbial diversity.


A comparison of complications of pregnancy and delivery in morbidly obese and non-obese women.
Morbid obesity in pregnancy is a growing problem and is having an impact on morbidity, mortality as well as significantly increasing antenatal and intra-partum costs of pregnancy care. The incidence of morbid obesity in pregnancy in our unit was 7.5% during the study period and this was associated with statistically significant increased maternal and perinatal morbidity. It also led to increased costs because of multidisciplinary management of the pregnancies, increased investigations and hospital stay when compared with normal weight pregnant women. Looking after morbidly obese pregnant women is an expensive undertaking, as the cost of the care of one morbidly obese pregnant woman and her baby is several times that of the normal weight woman. Health planners need to factor in these costs which are set to escalate given the predicted increase in the obese population in the UK.


Mechanobiology in cardiac physiology and diseases.
Mechanosensitivity is essential for heart function just as for all other cells and organs in the body, and it is involved in both normal physiology and diseases processes of the cardiovascular system. In this review, we have outlined the relationship between mechanosensitivity and heart physiology, including the Frank-Starling law of the heart and mechanoelectric feedback. We then focused on molecules involved in mechanotransduction, particularly mechanosensitive ion channels. We have also discussed the involvement of mechanosensitivity in heart diseases, such as arrhythmias, hypertrophy and ischaemic heart disease. Finally, mechanobiology in cardiogenesis is described with regard to regenerative medicine.


[Surgical treatment of aortic arch anomalies (author's transl)].
Anomalies of the aortic arch can be deducted by embryology. Aortic ring anomalies (double aortic arch, Art. lusoria, right descending aorta with Lig. arteriosum) have to be opened if clinically indicated. Aortic arch stenosis has to be removed by resection of intraaortic membranes, end-to-end-anastomosis, patch enlargement, or prosthetic bypass graft. Aortic interruptions require a functionally sufficient bridging by end-to-end-anastomosis, prosthetic bypass graft, or interposition of an aortic arch vessel. In 1971 the left common carotid artery was used in a 14 years old boy which seems to be insufficient for bridging the aortic arch defect five years later.


Association Between Delayed Graft Function and Graft Loss in Donation After Cardiac Death Kidney Transplants-A Paired Kidney Registry Analysis.
Delayed graft function (DGF) is an established complication after donation after cardiac death (DCD) kidney transplants, but the impact of DGF on graft outcomes is uncertain. To minimize donor variability and bias, a paired donor kidney analysis was undertaken where 1 kidney developed DGF and the other did not develop DGF using data from the Australia and New Zealand Dialysis and Transplant Registry. Using paired DCD kidney data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the association between DGF, graft and patient outcomes between 1994 and 2012 using adjusted Cox regression models. Of the 74 pairs of DCD kidneys followed for a median of 1.9 years (408 person-years), a greater proportion of recipients with DGF had experienced overall graft loss and death-censored graft loss at 3 years compared with those without DGF (14% vs 4%, P = 0.04 and 11% vs 0%, P < 0.01, respectively). Compared with recipients without DGF, the adjusted hazard ratio for overall graft loss at 3 years for recipients with DGF was 4.31 (95% confidence interval [95% CI], 1.13-16.44). The adjusted hazard ratio for acute rejection and all-cause mortality at 3 years in recipients who have experienced DGF were 0.98 (95% CI, 0.96-1.01) and 1.70 (95% CI, 0.36-7.93), respectively, compared with recipients without DGF. Recipients of DCD kidneys with DGF experienced a higher incidence of overall and death-censored graft loss compared with those without DGF. Strategies aim to reduce the risk of DGF could potentially improve graft survival in DCD kidney transplants.


A reorientation of clinical psychology? Look before you leap.
A recent proposal by Fox (1982) has suggested that the field of clinical psychology needs to undergo a reorientation away from psychopathology to the totality of human problems. This is viewed as a natural extension of the evolution of clinical psychology and is justified by the position that "Psychology is the only discipline that has both a comprehensive science of human behavior and an established professional arm" (Fox, 1982, p. 1052). Evidence is cited that suggests that many of the roles which Fox sees as appropriate for doctoral-level clinical psychologists can and are being performed adequately by master's-level professional social workers. The proposed reorientation of clinical psychology would be neither cost effective of educational resources nor feasible in terms of training adequate numbers of psychological service providers. This proposal by Fox further reflects a lack of awareness of the empirically based service tradition of many professional social workers (Thyer, 1981).


Urearetics: a small molecule screen yields nanomolar potency inhibitors of urea transporter UT-B.
Functional studies in knockout mice indicate a critical role for urea transporters (UTs) in the urinary concentrating mechanism and in renal urea clearance. However, potent and specific urea transport blockers have not been available. Here, we used high-throughput screening to discover high-affinity, small molecule inhibitors of the UT-B urea transporter. A collection of 50,000 diverse, drug-like compounds was screened using a human erythrocyte lysis assay based on UT-B-facilitated acetamide transport. Primary screening yielded approximately 30 UT-B inhibitors belonging to the phenylsulfoxyoxazole, benzenesulfonanilide, phthalazinamine, and aminobenzimidazole chemical classes. Screening of approximately 700 structurally similar analogs gave many active compounds, the most potent of which inhibited UT-B urea transport with an EC50 of approximately 10 nM, and approximately 100% inhibition at higher concentrations. Phenylsulfoxyoxazoles and phthalazinamines also blocked rodent UT-B and had good UT-B vs. UT-A specificity. The UT-B inhibitors did not reduce aquaporin-1 (AQP1)-facilitated water transport. In AQP1-null erythrocytes, "chemical UT-B knockout" by UT-B inhibitors reduced by approximately 3-fold UT-B-mediated water transport, supporting an aqueous pore pathway through UT-B. UT-B inhibitors represent a new class of diuretics, "urearetics," which are predicted to increase renal water and solute clearance in water-retaining states.


Glacial reduction and millennial-scale variations in Drake Passage throughflow.
The Drake Passage (DP) is the major geographic constriction for the Antarctic Circumpolar Current (ACC) and exerts a strong control on the exchange of physical, chemical, and biological properties between the Atlantic, Pacific, and Indian Ocean basins. Resolving changes in the flow of circumpolar water masses through this gateway is, therefore, crucial for advancing our understanding of the Southern Ocean's role in global ocean and climate variability. Here, we reconstruct changes in DP throughflow dynamics over the past 65,000 y based on grain size and geochemical properties of sediment records from the southernmost continental margin of South America. Combined with published sediment records from the Scotia Sea, we argue for a considerable total reduction of DP transport and reveal an up to ∼ 40% decrease in flow speed along the northernmost ACC pathway entering the DP during glacial times. Superimposed on this long-term decrease are high-amplitude, millennial-scale variations, which parallel Southern Ocean and Antarctic temperature patterns. The glacial intervals of strong weakening of the ACC entering the DP imply an enhanced export of northern ACC surface and intermediate waters into the South Pacific Gyre and reduced Pacific-Atlantic exchange through the DP ("cold water route"). We conclude that changes in DP throughflow play a critical role for the global meridional overturning circulation and interbasin exchange in the Southern Ocean, most likely regulated by variations in the westerly wind field and changes in Antarctic sea ice extent.


Oculodentodigital dysplasia. A case report.
This report describes a rare case of oculodentodigital (ODD) dysplasia, an autosomic-dominant disease with alteration on the gene GJA1 of connexin 43 on the human chromosome 6q22-q23, highlighting the anomalies affecting face, eyes, teeth and limbs. The case described shows bilateral microphthalmia, microcornea, syndactyly and other phenotypic alterations characteristic of this syndrome, such as: nose of reduced size with hypoplasic wings, partial stenosis of the choanae, micrognathia, ogival palate and hypoplasia of the enamel. The authors emphasize the importance to know the principal features of ODD syndrome in order to make a correct diagnosis and the role of the dentist in the treatment of this pathology.


Workplace Responses and Psychologists' Needs Following Client Suicide.
This research aimed to explore the role of workplace responses in psychologists' adaptation to client suicides. Participants were 178 psychologists who completed an online self-report questionnaire which included both open and closed questions yielding qualitative and quantitative data. Fifty-six (31.5%) participants reported one or more client suicides. Mixed results were found in terms of perceived support from the workplace following a client suicide. Psychologists reported a need for more open communication in the workplace, peer supports, space to grieve, as well as opportunities to engage in a learning process. The findings have important implications for research and for understanding the role of the workplace postvention. It also raises the need for external support to be accessible for psychologists working in private practice.


Psychosis in late life: emerging issues.
Psychotic symptoms in older individuals may be more common than was previously thought. Most kinds of psychosis that occur in younger people can be seen in older patients. However, there are important clinical differences between early-onset and late-onset psychosis. Conditions in which psychotic symptoms may occur in older adults include chronic illnesses such as dementia, schizophrenia, and delusional disorder, and acute transient disorders such as delirium and substance-induced psychosis. In this article, we focus on psychosis in chronic disorders in older individuals and discuss presentation and treatment of psychosis in patients with early-onset schizophrenia who have lived into old age, late-onset schizophrenia, very late-onset schizophrenia-like psychosis, delusional disorder, and Alzheimer's disease and other dementias.


Signaling in control of cell growth and metabolism.
Mammalian cells require growth-factor-receptor-initiated signaling to proliferate. Signal transduction not only initiates entry into the cell cycle, but also reprograms cellular metabolism. This instructional metabolic reprogramming is critical if the cell is to fulfill the anabolic and energetic requirements that accompany cell growth and division. Growth factor signaling mediated by the PI3K/Akt pathway plays a major role in regulating the cellular uptake of glucose, as well as the incorporation of this glucose carbon into lipids for membrane synthesis. Tyrosine-kinase-based regulation of key glycolytic enzymes such as pyruvate kinase also plays a critical role directing glucose carbon into anabolic pathways. In addition, the Myc transcription factor and mTOR kinase regulate the uptake and utilization of amino acids for protein and nucleic acid synthesis, as well as for the supply of intermediates to the mitochondrial Krebs cycle. However, the relationship between cellular signaling and metabolism is not unidirectional. Cells, by sensing levels of intracellular metabolites and the status of key metabolic pathways, can exert feedback control on signal transduction networks through multiple types of metabolite-derived protein modifications. These mechanisms allow cells to coordinate growth and division with their metabolic activity.


[Assessment of congenital foot deformities].
The assessment of congenital foot deformities is only relevant in the context of German legislation (SchwbG) defining disability and fitness for military service. All assessments of congenital foot deformities should be based on the twin concepts of function and capacity to withstand stress. However, assessments with regard to the degree of disability and fitness for military service will occasionally differ. This article discusses the various congenital foot deformities individually, allocating them to the respective degrees of disability [as laid down in German law]. The classification may serve as a guide for consultants within the context of disability legislation and for ascertaining fitness for military service in accordance with the "Central Standing Orders" of the Federal German armed forces.


Primary Care Provider Views About Usefulness and Dissemination of a Web-Based Depression Treatment Information Decision Aid.
Decisions related to mental health are often complex, problems often remain undetected and untreated, information unavailable or not used, and treatment decisions frequently not informed by best practice or patient preferences. The objective of this paper was to obtain the opinions of health professionals working in primary health care settings about a Web-based information decision aid (IDA) for patients concerning treatment options for depression and the dissemination of the resources in primary care settings. Participants were recruited from primary care clinics in Winnipeg and Ottawa, Canada, and included 48 family physicians, nurses, and primary care staff. The study design was a qualitative framework analytic approach of 5 focus groups. Focus groups were conducted during regular staff meetings, were digitally recorded, and transcripts created. Analysis involved a content and theme analysis. Seven key themes emerged including the key role of the primary care provider, common questions about treatments, treatment barriers, sources of patient information, concern about quality and quantity of available information, positive opinions about the IDA, and disseminating the IDA. The most common questions mentioned were about medication and side effects and alternatives to medication. Patients have limited access to alternative treatment options owing to cost and availability. Practitioners evaluated the IDA positively. The resources were described as useful, supportive of providers' messages, and accessible for patients. There was unanimous consensus that information needs to be available electronically through the Internet.


Sooty molds from the Jurassic of Patagonia, Argentina.
The sooty molds are a globally distributed ecological group of ascomycetes with epiphyllous, saprotrophic habit, comprising several phylogenetically distant taxa (i.e., members of the classes Dothideomycetes and Eurotiomycetes). Their fossil record extends almost continuously back to the early Cretaceous; however, they are hypothesized to have originated in the early Mesozoic. Here, we describe new specimens of sooty molds associated with conifer leaves from Jurassic hot spring deposits of Patagonia, Argentina. Thin sections of chert samples from the La Matilde Formation, Deseado Massif (Santa Cruz, Argentina) were observed using light microscopy. The fungi occur on the surface and axils of leafy twigs with podocarpaceous affinities, forming dense subicula comprised by opaque moniliform hyphae. Additionally, several asexual and sexual reproductive structures are observed. On the basis of vegetative (i.e., dense subicula composed of moniliform hyphae; hyphae composed of opaque cells deeply constricted at the septa) and reproductive characters (i.e., poroconidial and sympodioconidial asexual stages and diverse spores), two morphotypes were identified with affinities within lineages of the subphylum Pezizomycotina that encompass the ecological group of sooty molds, and a third morphotype was within the phylum Ascomycota. This finding extends the fossil record of sooty molds to the Jurassic and their geographic fossil range to the South American continent. In particular, their association with podocarpaceous conifers is shown to be ancient, dating back to the Jurassic. This new record provides an additional reference point on the diversity of interactions that characterized Jurassic forests in Patagonia.


Pd-PEPPSI-IHept(Cl) : A General-Purpose, Highly Reactive Catalyst for the Selective Coupling of Secondary Alkyl Organozincs.
Dichloro[1,3-bis(2,6-di-4-heptylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(II) (Pd-PEPPSI-IHept(Cl) ), a new, very bulky yet flexible Pd-N-heterocyclic carbene (NHC) complex has been evaluated in the cross-coupling of secondary alkylzinc reactants with a wide variety of oxidative addition partners in high yields and excellent selectivity. The desired, direct reductive elimination branched products were obtained with no sign of migratory insertion across electron-rich and electron-poor aromatics and all forms of heteroaromatics (five and six membered). Impressively, there is no impact of substituents at the site of reductive elimination (i.e., ortho or even di-ortho), which has not yet been demonstrated by another catalyst system to date.


Advances and Applications of Atomic-Resolution Scanning Transmission Electron Microscopy.
Although scanning transmission electron microscopy (STEM) images of individual heavy atoms were reported 50 years ago, the applications of atomic-resolution STEM imaging became wide spread only after the practical realization of aberration correctors on field-emission STEM/TEM instruments to form sub-Ångstrom electron probes. The innovative designs and advances of electron optical systems, the fundamental understanding of electron–specimen interaction processes, and the advances in detector technology all played a major role in achieving the goal of atomic-resolution STEM imaging of practical materials. It is clear that tremendous advances in computer technology and electronics, image acquisition and processing algorithms, image simulations, and precision machining synergistically made atomic-resolution STEM imaging routinely accessible. It is anticipated that further hardware/software development is needed to achieve three-dimensional atomic-resolution STEM imaging with single-atom chemical sensitivity, even for electron-beam-sensitive materials. Artificial intelligence, machine learning, and big-data science are expected to significantly enhance the impact of STEM and associated techniques on many research fields such as materials science and engineering, quantum and nanoscale science, physics and chemistry, and biology and medicine. This review focuses on advances of STEM imaging from the invention of the field-emission electron gun to the realization of aberration-corrected and monochromated atomic-resolution STEM and its broad applications.


[Urticaria and mast cells in adolescence].
Adolescent patients are often affected by dermographic, cholinergic, cold or solar urticaria brought about by distinct physical stimulation. These physical forms of urticaria as well as cutaneous and systemic mastocytosis are due to the release of inflammatory mediators from the mast cells. As these diseases usually show characteristic cutaneous symptoms, they can easily be distinguished from other subtypes of urticarial reaction. In order to make the reader familiar with physical urticaria and mastocytosis, we describe the clinical features, pathogenic factors, and therapeutic possibilities of these disorders in adolescence.


Clinical experience of methotrexate in Crohn's disease: response, safety and monitoring of treatment.
Methotrexate is an immunosuppressant used in the treatment of patients with Crohn's disease who are intolerant or refractory to azathioprine. To present clinical experience in terms of response, side effects and reason for cessation of methotrexate treatment as well as adherence to monitoring regimens. Retrospective review of case records of 37 patients taking methotrexate for Crohn's disease at the Bristol Royal Infirmary, a large UK teaching hospital. Thirty-five patients used oral methotrexate. Response rate to methotrexate was 78% at 3 months. Adverse events were uncommon and rarely dangerous. Monitoring of treatment did not adhere to British Society of Gastroenterology guidelines. Oral methotrexate is effective and safe in the treatment of Crohn's disease. This is in contrast to findings of previous series, which have mainly reported on intramuscular methotrexate use. Monitoring of treatment is currently inadequate and consensus should be sought for a pragmatic monitoring schedule to resolve this important governance issue.


Vestibular Function in Children With a Congenital Cytomegalovirus Infection: 3 Years of Follow-Up.
Congenital cytomegalovirus (cCMV) infection is the most common nongenetic cause of sensorineural hearing loss in children. Due to the close anatomical relationship between the auditory and the vestibular sensory organs, cCMV can also be an important cause of vestibular loss. However, the prevalence and nature of cCMV-induced vestibular impairment is still underexplored. The aim of this study was to investigate the occurrence and characteristics of vestibular loss in a large group of cCMV-infected children, representative of the overall cCMV-population. Ninety-three children (41 boys, 52 girls) with a confirmed diagnosis of cCMV were enrolled in this prospective longitudinal study. They were born at the Ghent University Hospital or referred from another hospital for multidisciplinary follow-up in the context of cCMV. The test protocol consisted of regular vestibular follow-up around the ages of 6 months, 1 year, 2 years, and 3 years with the video Head Impulse Test, the rotatory test, and the cervical Vestibular Evoked Myogenic Potential test. On average, the 93 patients (52 asymptomatic, 41 symptomatic) were followed for 10.2 months (SD: 10.1 mo) and had 2.2 examinations (SD: 1.1). Seventeen (18%) patients had sensorineural hearing loss (7 unilateral, 10 bilateral). Vestibular loss was detected in 13 (14%) patients (7 unilateral, 6 bilateral). There was a significant association between the occurrence of hearing loss and the presence of vestibular loss (p < 0.001), with 59% (10/17) vestibular losses in the group of hearing-impaired children compared to 4% (3/76) in the group of normal-hearing subjects. In the majority of the cases with a vestibular dysfunction (85%, 11/13), both the semicircular canal system and the otolith system were affected. The remaining subjects (15%, 2/13) had an isolated semicircular canal dysfunction. Sixty-one patients already had at least one follow-up examination. Deterioration of the vestibular function was detected in 6 of them (10%, 6/61). cCMV can impair not only the auditory but also the vestibular function. Similar to the hearing loss, vestibular loss in cCMV can be highly variable. It can be unilateral or bilateral, limited or extensive, stable or progressive, and early or delayed in onset. As the vestibular function can deteriorate over time and even normal-hearing subjects can be affected, vestibular evaluation should be part of the standard otolaryngology follow-up in all children with cCMV.


Studies concerning the hypercholesterolemia of pregnancy: cholesterol catabolism and excretion during late pregnancy in the rat.
To investigate the mechanism of hypercholesterolemia noted in pregnancy, cholesterol catabolism and excretion was investigated during late pregnancy in the rat. Pregnancy was associated with an increase in plasma cholesterol and a decrease in the concentration of both cholesterol and bile acids in bile (with no difference in bile flows). The appearance of injected 4-C14-cholesterol in the bile of pregnant females was less than that of virgin females with a significant decrease in the bile acid fraction. The cholic/chenodeoxycholic acid ratio of newly formed C14 bile acids in pregnant rat bile was lower than in the bile of virgin female rats. Surprisingly, cholesterol balance studies failed to reveal any difference in the fecal excretion of neutral sterols or bile acids between virgin and pregnant female rats. The hypercholesterolemia of pregnancy could be partially due to the decrease in biliary cholesterol and bile acid excretion. The lack of difference in fecal cholesterol excretion is perhaps due to the operation of compensatory absorption mechanisms in the intestine which needs further investigation.


Specific brain networks during explicit and implicit decoding of emotional prosody.
To better define the underlying brain network for the decoding of emotional prosody, we recorded high-resolution brain scans during an implicit and explicit decoding task of angry and neutral prosody. Several subregions in the right superior temporal gyrus (STG) and bilateral in the inferior frontal gyrus (IFG) were sensitive to emotional prosody. Implicit processing of emotional prosody engaged regions in the posterior superior temporal gyrus (pSTG) and bilateral IFG subregions, whereas explicit processing relied more on mid STG, left IFG, amygdala, and subgenual anterior cingulate cortex. Furthermore, whereas some bilateral pSTG regions and the amygdala showed general sensitivity to prosody-specific acoustical features during implicit processing, activity in inferior frontal brain regions was insensitive to these features. Together, the data suggest a differentiated STG, IFG, and subcortical network of brain regions, which varies with the levels of processing and shows a higher specificity during explicit decoding of emotional prosody.


The microbiome of the marine flatworm Macrostomum lignano provides fitness advantages and exhibits circadian rhythmicity.
The close association between animals and their associated microbiota is usually beneficial for both partners. Here, we used a simple marine model invertebrate, the flatworm Macrostomum lignano, to characterize the host-microbiota interaction in detail. This analysis revealed that the different developmental stages each harbor a specific microbiota. Studies with gnotobiotic animals clarified the physiological significance of the microbiota. While no fitness benefits were mediated by the microbiota when food was freely available, animals with microbiota showed significantly increased fitness with a reduced food supply. The microbiota of M. lignano shows circadian rhythmicity, affecting both the total bacterial load and the behavior of specific taxa. Moreover, the presence of the worm influences the composition of the bacterial consortia in the environment. In summary, the Macrostomum-microbiota system described here can serve as a general model for host-microbe interactions in marine invertebrates.


Cyclosporine A inhibits the activity of a TATA box-binding protein that is required for transcription from the adenovirus major late promoter.
Nuclear extracts from P1798 lymphoma cells support transcription from the adenovirus major late promotor (AdMLP) and the human histone H4 promoter. Nuclear extracts prepared from P1798 cells treated with 1 microgram/ml cyclosporine A for 24 h fail to support transcription from AdMLP, whereas transcription from the histone H4 promoter is unimpaired. Both control and cyclosporine-treated extracts contain proteins that interact with synthetic deoxyoligonucleotides that correspond to the CAAT box, TATA box, and upstream stimulatory element of AdMLP. Cyclosporine had no discernible qualitative or quantitative effect upon such DNA-protein interactions, as observed by gel mobility shift assays. Analysis of 5' deletion mutants of AdMLP indicates that deletion of sequences upstream of the TATA box reduces AdMLP transcription by only 50%. This observation suggests that cyclosporine A, which inhibits AdMLP transcription by > 90%, is unlikely to act through changes in the amount or activity of upstream activators such as upstream stimulatory factor- or CAAT box-binding proteins. On the other hand, deletion of TATA box sequences between -50 and -11 base pairs virtually eliminates transcription from AdMLP in vitro. A partially purified TFIID fraction was obtained from control P1798 nuclear extracts. The TFIID fraction reconstitutes transcription from AdMLP when added to extracts from cyclosporine A-treated cells. Recombinant TATA box-binding protein also reconstitutes transcription from AdMLP in cyclosporine A-treated extracts. These results are consistent with the hypothesis that cyclosporine A regulates the activity of a subset of general transcription factors which are required for initiation from some promoters (such as AdMLP) but not from others (such as histone H4).


Spin crossover phenomena in long chain alkylated complexes.
Soft materials represented by polymers, liquid crystals, and colloids are a class of materials that exhibit a variety of unique functionalities which derive from their non-rigid structures. In particular, soft metal complexes incorporating flexible long alkyl chains in their structures have been shown to display synergy between the structural dynamics of the long alkyl chain moieties and the electron dynamics occurring at the metal centre. This review presents a discussion of such soft metal complexes with a focus on spin crossover (SCO) behaviours that are associated with a structural phase transition, including a liquid crystal (LC) transition, arising from the flexible natures of the respective complexes. We also discuss how to fabricate soft materials based on SCO complexes.


Incidence of Early Adverse Events After Tibial Tubercle Osteotomy.
Tibial tubercle osteotomy (TTO) is a commonly utilized surgical procedure for the treatment of patellofemoral instability. Although midterm and long-term outcomes are known, perioperative complications have not been consistently reported. To identify the incidence and predictors of adverse events in the first 90-day perioperative period after TTO. Case series; Level of evidence, 4. Patients undergoing primary TTO between January 1, 2010, and December 31, 2019, were included. Readmissions in the first 90 days after surgery were collected, and data were collected for the following variables: age, sex, smoking status, body mass index, laterality, preoperative diagnosis, presence of trochlear dysplasia, tourniquet use, TTO procedure, tibial tubercle distalization, trochleoplasty, chondral procedure, number of screws, and use of an epidural catheter. Predictors of readmission for any reason were identified using multivariable logistic regression analysis. A total of 345 TTO procedures were included in the final analysis. The incidence of readmissions for any reason was 20.6% (71/345). The most common reason for readmission was postoperative pain (26/345 [7.5%]), followed by wound complications (19/345 [5.5%]) and epidural catheter-related complications (overall: 16/345 [4.6%]; specific: 16/167 [9.6%]. The incidence of major complications was 2.0% (7/345). The number of patients with each major complication was as follows: 1 for deep vein thrombosis, 2 for pulmonary embolism, 1 for septic arthritis, 1 for tibial tubercle fracture, and 2 for loss of fixation. Female sex and smoking were associated with readmission for pain. The incidence of major complications after TTO was very low (2.0%), but 20.6% of cases required readmission, primarily for an indwelling epidural catheter (3.5%) and postoperative pain (7.5%). Concomitant soft tissue procedures and the number of screws were associated with readmission after TTO. Utilizing individualized postoperative pain management and preoperative discussions about expected pain may help to avoid readmission for pain after TTO.


Relationship between immunological rejection and matrix GLA protein in cryopreserved vascular allografts.
Cryopreserved tissue allografts used for cardiovascular diseases become calcified as a late complication after transplantation, probably caused by immunological rejection. Recent attention has been focused on the inhibitory effect of matrix Gla protein (MGP) on ectopic vascular calcification, but the behavior of MGP in cryopreserved allografts is uncertain. In this study we examined the relationship between immunological rejection and MGP in cryopreserved rat aortic grafts after transplantation. Cryopreserved rat aortae were isografted or allografted intraperitoneally. Fresh isografts were also tested. The grafts were retrieved 9 days after transplantation and the intragraft MGP mRNA was measured by a real-time quantitative PCR method. The effect of daily administration of FK506 on MGP mRNA levels in cryopreserved isografts and allografts after transplantation was also evaluated. There was no significant difference in intragraft MGP mRNA levels between fresh and cryopreserved isografts 9 days after transplantation. MGP expression levels in cryopreserved allografts were significantly lower as compared to those in cryopreserved isografts (P < .01). Daily administration of FK506 enhanced intragraft MGP mRNA (ninefold) in cryopreserved allografts (P < .01), but not in cryopreserved isografts. Immunological rejection is likely to inhibit MGP expression in cryopreserved vascular allografts, resulting in late-onset calcification.


Cardiovascular and neurohormonal effects of atrial natriuretic peptide in conscious dogs with and without chronic left ventricular dysfunction.
Atrial natriuretic peptide (hANP 4-28) was infused for 1 h (0.3 microgram/kg/min) in 11 normal awake dogs and seven awake dogs with chronic left ventricular dysfunction, induced 16 weeks earlier by repetitive DC shock. The responses were similar in the two groups and included decreases in arterial pressure (107-99 mm Hg), heart rate (83-72 beats/min), and cardiac output (3.6-2.8 L/min), without changes in right or left ventricular filling pressures. Systemic vascular resistance (SVR) tended to rise during the infusion and was significantly increased (2,847-3,442 dyn s cm-5, p less than .05) during the postinfusion recovery period. Regional blood flows (microspheres) during infusion revealed a decrease in skin and splanchnic flow. Despite the apparent vasoconstrictor effect, plasma norepinephrine (PNE), renin activity (PRA), and arginine vasopressin (AVP) levels all fell during ANP infusion. These data suggest that ANP exerts a cardioinhibitory effect, possibly similar to that of arginine vasopressin (AVP), and that the net systemic vasoconstrictor effect of ANP in these dogs is mediated by a complex interrelationship between direct vascular effects, neurohormonal inhibition, and central reflex activation.


Exploring the drivers of population structure across desert snakes can help to link micro and macroevolution.
To understand the underlying mechanisms generating population genetic divergence and structure is a critical step towards understanding how biodiversity evolves at both micro- and macroevolutionary scales. At the population-level, geographic isolation as well as adaptation to local environmental conditions can generate different patterns of spatial genetic variation among populations. Specific organismal traits as well as the characteristics of the environment might influence the process under which populations become spatially structured. In a From the Cover article in this issue of Molecular Ecology, Myers et al. (2019) present an integrative approach to investigate if the Cochise filter barrier (CFB), lying between the Sonoran and Chihuahuan Deserts, and the surrounding river networks were relevant in driving the population structure of 13 snake species. While local environmental conditions seem to predominantly contribute to lineage divergence, traditionally studied vicariant barriers seem to have played a minor role in shaping population structure across the studied species. This study brings insights into how population-level processes could contribute to the formation of incipient species, which ultimately might affect the speciation rates measured at macroevolutionary scales. Hence, Myers et al. (2019) not only represents an integrative study aiming to understand the drivers of population genetic divergence, but also a potentially important contribution to our ongoing challenge in linking micro- and macroevolution.


ProfNet, a method to derive profile-profile alignment scoring functions that improves the alignments of distantly related proteins.
Profile-profile methods have been used for some years now to detect and align homologous proteins. The best such methods use information from the background distribution of amino acids and substitution tables either when constructing the profiles or in the scoring. This makes the methods dependent on the quality and choice of substitution table as well as the construction of the profiles. Here, we introduce a novel method called ProfNet that is used to derive a profile-profile scoring function. The method optimizes the discrimination between scores of related and unrelated residues and it is fast and straightforward to use. This new method derives a scoring function that is mainly dependent on the actual alignment of residues from a training set, and it does not use any additional information about the background distribution. It is shown that ProfNet improves the discrimination of related and unrelated residues. Further it can be used to improve the alignment of distantly related proteins. The best performance is obtained using superfamily related proteins in the training of ProfNet, and a classifier that is related to the distance between the structurally aligned residues. The main difference between the new scoring function and a traditional profile-profile scoring function is that conserved residues on average score higher with the new function.


Sustained Diurnal Stimulation of Cyclic Electron Flow in Two Tropical Tree Species Erythrophleum guineense and Khaya ivorensis.
The photosystem II (PSII) activity of C3 plants is usually inhibited at noon associated with high light but can be repaired fast in the afternoon. However, the diurnal variation of photosystem I (PSI) activity is unknown. Although, cyclic electron flow (CEF) has been documented as an important mechanism for photosynthesis, the diurnal variation of CEF in sun leaves is little known. We determined the diurnal changes in PSI and PSII activities, light energy dissipation in PSII and the P700 redox state in two tropical tree species Erythrophleum guineense and Khaya ivorensis grown in an open field. The PSI activity (as indicated by the maximum quantity of photo-oxidizable P700) was maintained stable during the daytime. CEF was strongly activated under high light at noon, accompanying with high levels of non-photochemical quenching (NPQ) and PSI oxidation ratio. In the afternoon, CEF was maintained at a relatively high level under low light, which was accompanied with low levels of NPQ and P700 oxidation ratio. These results indicated that CEF was flexibly modulated during daytime under fluctuating light conditions. Under high light at noon, CEF-dependent generation of proton gradient across the thylakoid membranes (ΔpH) mainly contributed to photoprotection for PSI and PSII. By comparison, at low light in the afternoon, the CEF-dependent formation of ΔpH may be important for PSII repair via an additional ATP synthesis.


A cumulative experience examining the effect of natural and synthetic antimicrobial peptides vs. Chlamydia trachomatis.
We tested the activity of 48 structurally diverse antimicrobial peptides against Chlamydia trachomatis, serovar L2. The peptides' activity against C. trachomatis, serovar L2 was measured in 48-h McCoy cell shell vial assays. Peptides of 16-20 amino acids were more active than larger peptides, such as defensins. Beta-sheet protegrins, as well as alpha-helical peptides such as novispirin (G-10) were equally active. Enantiomers were as active as native structures. Moderate-sized circular mini-defensins were less effective against C. trachomatis. Moderate-sized cationic peptides may be useful in microbicide preparations designed to prevent chlamydial infection.


Venous Doppler ultrasound assessment of the parasellar region.
The purpose of this report is to present normal values for venous blood flow velocities from the parasellar region using transcranial Doppler ultrasound (2-MHz transducer) with both transtemporal and transorbital approaches and to examine the nature of previously reported low-pulsatility signals with velocities in the arterial range from this area. Forty-three subjects ranging in age from 18 to 56 years (mean +/- SD, 31.9 +/- 10.1 years) were examined. In all subjects, a venous signal directed away from the probe with the source lateral to the internal carotid artery siphon was detected on at least one side. A total of 72 parasellar venous signals were insonated. Signals were considered to belong to the main inflow and outflow vessels of the cavernous sinus. The mean blood flow velocity ranged from 6 to 81 cm/s (mean +/- SD, 27.3 +/- 17.4 cm/s). Typical transients in the Valsalva test confirmed the venous character of the signals. No significant gender, side-to-side or age dependency was observed. A separate analysis was done for venous high-velocity signals defined by a mean blood flow velocity greater than 30 cm/s. They were detected in 21 out of 43 subjects (48.9%) via a transtemporal approach and in 6 of them (14%) via the transorbital route, too. Again, no significant gender, side-to-side or age dependency was noted. In summary, we found a greater variability of venous blood flow velocities in the parasellar region compared to other basal cerebral veins, e.g. the basal vein of Rosenthal. The previously reported low-pulsatility signals with velocities in the arterial range proved to be of venous origin.


VARIATION IN SPECIES DIVERSITY AND SHELL SHAPE IN HAWAIIAN LAND SNAILS: IN SITU SPECIATION AND ECOLOGICAL RELATIONSHIPS.
The native land-snail fauna of the Hawaiian islands was investigated from a combined perspective of ecological and historical, vicariant, and dispersalist biogeography. There were more than 750 described, valid species; almost all were endemic to the archipelago, many to single islands. Path analysis showed that island area, per se, had the strongest influence on numbers of species. Island altitude and number of plant communities, both strongly related to area and both dimensions of habitat diversity, also had major influences. The influence of island age was complex. A direct effect, older islands having more species, was more than counterbalanced by the strong indirect effects of age on area and altitude: older islands are smaller and lower, and smaller, lower islands had fewer species. Distance of an island from a source of colonization was of minor importance. Species richness thus appears to be related almost exclusively to evolutionary radiation in situ and not to an equilibrium between immigration and extinction. Islands need not be extremely isolated for evolutionary radiation to be more important than immigration/extinction dynamics in determining species richness, but isolation is a relative term dependent on the dispersal abilities of the organisms in question. Numbers of recorded species were also strongly correlated with collecting effort on each island, a result that stands as a warning to others involved in such studies. Numbers of species in different families were not evenly distributed across islands. Notably, Kauai had more amastrids and helicinids and fewer achatinellids than predicted; Oahu had more amastrids but fewer pupillids and succineids than predicted; Hawaii exhibited the opposite pattern from Oahu. These patterns may partly reflect the vagaries of collecting/describing effort, but some may be due to the combined effects of historical factors and competitive exclusion. The distribution of shell height/diameter was bimodal with a distinct absence of more or less equidimensional species, a general pattern seen in other faunas. Among the pulmonates, tall species predominated, suggesting a relative lack of opportunity for globular/flat species. Notably, amastrids occurred in both modes, evidence that, at least in part, ecological not taxonomic factors underlie the bimodality. The proportions of tall and globular/flat species did not vary among islands. Prosobranchs were mostly low-spired but generally less flat than the pulmonates in the low-spired mode. The islands were probably colonized originally by small taxa. Large, tall shells are found only on Kauai and Niihau, the oldest of the main islands, suggesting that opportunities for such species are probably available on other islands.


MRI-guided and ultrasound-triggered release of NO by advanced nanomedicine.
Nitric oxide (NO) has been well identified as a specific free radical molecule possessing wide-ranging therapeutic effects. Targeted delivery and controlled release of NO are highly desired to realize precision gas therapy, but are still challenging owing to the non-targetability and uncontrollability of NO itself. Herein, we propose a new concept of MRI-guided and ultrasound-triggered gas release for precision gas therapy. Based on this concept, we develop a novel ultrasound-responsive BNN-type NO-releasing molecule (NORM) and an advanced rattle-type nano-carrier of superparamagnetic iron oxide-encapsulated mesoporous silica nanoparticles (SPION@hMSN), and use them to construct a new intelligent nanomedicine (BNN6-SPION@hMSN) for the first time. The BNN6-SPION@hMSN nanomedicine exhibits excellent passive tumor-targeting capability, high MRI-guided tumor localization performance and a unique ultrasound-triggered NO release profile. The tumor-targeted, MRI-guided and ultrasound-triggered release profiles of the developed nanomedicine enable the tumor site-specific controlled release of NO in favor of high-efficacy and safe NO gas therapy of tumor.


Ethnic, Racial, and Socioeconomic Disparities in Retinoblastoma.
Most children with retinoblastoma in the United States are diagnosed as having a large intraocular tumor burden that requires intensive ocular-salvage treatment or enucleation. To investigate the effect of socioeconomic status, race, and ethnicity on the extent of disease and the outcomes of retinoblastoma. A population-based review of 18 Surveillance, Epidemiology, and End Results (SEER) registries. From January 1, 2000, through December 31, 2010, 830 cases of retinoblastoma were recorded for children aged 0 to 9 years. Data were collected and analyzed from January 1, 2000, through December 31, 2010, with the last follow-up on December 31, 2010. County-based socioeconomic variables analyzed included poverty level, educational attainment, language isolation, crowding, unemployment, and percentage of immigrants. Extent of disease, ocular outcome, and children's survival. Of the 830 individuals included, Hispanic children had a higher percentage of extraocular disease (86 of 261 [33.0%] vs. 102 of 510 non-Hispanic children [20.0%]; odds ratio [OR], 1.97 [95% CI, 1.38-2.79]). The percentage of extraocular cases was also higher in counties with the following low socioeconomic status indicators: higher vs. lower poverty status (115 of 413 [27.8%] vs. 73 of 358 [20.4%]; OR, 1.51; 95% CI, 1.06-2.14); lower vs. higher educational attainment (115 of 400 [28.7%] vs. 73 of 371 [19.7%]; OR, 1.65; 95% CI, 1.16-2.34); higher vs. lower levels of crowding (124 of 398 [31.2%] vs. 64 of 373 [17.2%]; OR, 2.18; 95% CI, 1.53-3.13); higher vs. lower unemployment (119 of 411 [28.9%] vs. 69 of 360 [19.2%]; OR, 1.72; 95% CI, 1.21-2.45); higher vs. lower language isolation (117 of 388 [30.2%] vs. 71 of 383 [18.5%]; OR, 1.89; 95% CI, 1.34-2.70); and higher vs. lower percentage of immigrants (109 of 386 [28.2%] vs. 79 of 385 [20.5%]; OR, 1.52; 95% CI, 1.08-2.16). Higher rates of enucleation were associated with low educational attainment (265 of 401 [66.1%] vs 309 of 421 [73.4%]; OR, 1.42; 95% CI, 1.04-1.93), a higher level of crowding (316 of 416 [76.0%] vs. 258 of 406 [63.5%]; OR, 1.81; 95% CI, 1.32-2.48), and Hispanic origin (202 of 271 [74.5%]; OR, 1.41; 95% CI, 1.01-1.98). Relative survival at 5 years was lower among black compared with non-Hispanic white children (92.7% vs. 99.2%; P < .001). Significant disparities exist in the care and outcomes of children with retinoblastoma. A low socioeconomic status negatively affects disease extent and ocular outcomes, presumably by limiting access to primary and cancer-directed care. Hispanic children in particular have more advanced disease and higher rates of enucleation.


CHOROIDAL NEOVASCULARIZATION AND CHORIORETINAL ATROPHY IN A PATIENT WITH MELANOMA-ASSOCIATED RETINOPATHY AFTER IPILIMUMAB/NIVOLUMAB COMBINATION THERAPY.
To describe a case of choroidal neovascularization (CNV) and chorioretinal scarring in a patient with melanoma-associated retinopathy after ipilimumab/nivolumab combination immune therapy for malignant melanoma. Retrospective case report with fundus photography, fluorescein angiography, optical coherence tomography, and electroretinography. A 65-year-old woman presented with symptoms of photopsia and visual field loss. She had previously undergone ipilimumab/nivolumab combination chemotherapy treatment for malignant melanoma 14 months earlier coinciding with the onset of her visual symptoms. Fundus photography showed bilateral atrophic chorioretinal lesions and peripheral retinal pigment epithelial changes. Fluorescein angiography revealed retinovascular leakage in both eyes with CNV in the right eye. Optical coherence tomography showed a pigment epithelial detachment with subretinal fluid and subretinal hyperreflective material consistent with occult CNV. Visual field testing showed generalized visual field loss in both eyes. Bloodwork discovered an elevated angiotensin-converting enzyme. Electroretinography revealed abnormal peripheral rod and cone function with impairment of the photoreceptor and inner nuclear layer. Serum Western blot was positive for 60 kDa antiretinal autoantibody. After a single bevacizumab injection in the right eye, CNV resolved and visual acuity improved from 20/50 before the injection to 20/25 3 months after the injection. Visual acuity in the left eye deteriorated for months to counting fingers but then improved to 20/100 on follow-up examinations. Ipilimumab and nivolumab have been associated with immune-related ocular adverse effects. We report a case of combination therapy presenting with chorioretinal scarring and subsequent CNV in a patient with melanoma-associated retinopathy, a rare yet important adverse effect.


Dynamic evaluation of the comparative effectiveness of an integrated program for heart failure care.
An integrated care program for heart failure (HF) was developed in the Basque Country in 2013. The objective of this research was to evaluate its effectiveness through the number of hospital admissions in three integrated healthcare organizations (IHOs), taking into account the longitudinal nature of the disease and the intensity of the implementation. A retrospective observational study was carried out, based on data entered in administrative and clinical databases between 2014 and 2018 for a total population of 230 000. In addition to conventional statistical analyses, Andersen-Gill models for recurrent events were used, incorporating dynamic variables that allowed assessment of the intervention's intensity before each hospitalization. A total of 6768 patients were analysed. Age (hazard ratio [HR] = 1.016; 95% confidence interval [CI] 1.011-1.022), the Charlson index (HR = 1.067, 95% CI 1.047-1.087), and the number of previous hospitalizations (HR = 1.632, 95% CI 1.557-1.712) were risk factors for readmission. Differences between IHOs were also statistically significant. Greater intervention intensity was associated with a lower hospitalization rate (HR = 0.995, 95% CI 0.990-1.000). As indicated by the interaction between intervention intensity and IHO, differences between IHOs disappeared when intensity rose. No inequities in hospitalization were found as a function of deprivation index or sex. Nonetheless, inequity in the implementation of the program by sex was clear, women with HF receiving less intense intervention than men with the same level of comorbidity and age. The extent of program implementation measured by intervention intensity is a main driver of the effectiveness of an educational and monitoring program for HF. The evaluation of HF program effectiveness on readmissions must take into account the entire natural history of the disease. Implementation intensity explains differences between IHOs.


Comprehensive Analysis of MicroRNA⁻Messenger RNA from White Yak Testis Reveals the Differentially Expressed Molecules Involved in Development and Reproduction.
Testis development is a vital and tightly regulated process in mammals. Understanding the biological mechanisms underlying testis development will benefit the animal reproduction industry. Expression changes in microRNA and messenger RNA in response to dynamic regulation effects have been associated with this process. However, very little is known about the roles of these molecules in yak development. Using whole-genome small RNA and messenger RNA sequencing, we performed a comprehensive analysis of the microRNA⁻messenger RNA interaction network expression in the testicles of Tianzhu white yaks during three developmental stages. Using Short Time-series Expression Miner analysis we identified 589 differentially expressed microRNAs (DERs) and 3383 differentially expressed messenger RNAs (DEGs) in the three age groups. A total of 93 unique DEGs are primarily involved in reproduction and testis development. Subsequently, four integration networks were constructed according to the DEGs and DERs in three biological processes. Nineteen DEGs were potentially regulated by 60 DERs, of which miR-574 and target gene AURKA played a crucial role in yak testis development and reproduction. The results of this study provide a basis for further exploration of the microRNA⁻messenger RNA interactions in testis development and reproduction and aid in uncovering the molecular mechanisms of spermatogenesis in male mammals.


Preventing Thin Film Dewetting via Graphene Capping.
A monolayer 2D capping layer with high Young's modulus is shown to be able to effectively suppress the dewetting of underlying thin films of small organic semiconductor molecule, polymer, and polycrystalline metal, respectively. To verify the universality of this capping layer approach, the dewetting experiments are performed for single-layer graphene transferred onto polystyrene (PS), semiconducting thienoazacoronene (EH-TAC), gold, and also MoS2 on PS. Thermodynamic modeling indicates that the exceptionally high Young's modulus and surface conformity of 2D capping layers such as graphene and MoS2 substantially suppress surface fluctuations and thus dewetting. As long as the uncovered area is smaller than the fluctuation wavelength of the thin film in a dewetting process via spinodal decomposition, the dewetting should be suppressed. The 2D monolayer-capping approach opens up exciting new possibilities to enhance the thermal stability and expands the processing parameters for thin film materials without significantly altering their physical properties.


Daily and weekly iron supplementation and physical growth of school age Indonesian children.
To investigate the effect of 3 months iron supplementation on physical growth among anemic school children given daily and weekly and to know the response based on hemoglobin level. One hundred forty-four children were measured for height, weight and hemoglobin level. Ninety seven children were anemic (67.36%) with Hb level < 12 g/dl and forty seven children were non anemic. anemic children were divided into 2 subgroups and randomly assigned to either daily and weekly Fe treatment for 12 weeks. The non anemic group were treated with weekly iron supplementation, which was accepted by the parents. Children's height, weight, and hemoglobin of T1 and T2 food recall method was used to know calorie, protein, vitamin C and iron intake in both daily and weekly subgroups. Three days food recall was performed in the second and third months by a nutritionist. After iron supplementation, the hemoglobin level in both group increased significantly. The average change of hemoglobin between the 2 groups gave no significant difference. W/A and H/A after iron supplementation showed significantly increased in both groups. The average change of W/A and H/A between the 2 groups gave no significant difference. Daily and weekly iron supplementation showed no significant difference in increasing of hemoglobin level and physical growth. Further research must be done with appropriate sample size and well design.


Phodopus campbelli detect reduced photoperiod during development but, unlike Phodopus sungorus, retain functional reproductive physiology.
Golden (Mesocricetus auratus) and Siberian (Phodopus sungorus) hamsters are widely used as animal models for seasonal reproduction; but M. auratus shows no developmental delay in short days until after sexual maturity, whereas P. sungorus juveniles delay development in short days. As the photoperiodic response of Phodopus campbelli is not well established, litters of the two Phodopus species were gestated and reared under long days (14 h light:10 h darkness) or short days (10 h light:14 h darkness) until 70 days of age. As expected, under short photoperiod P. sungorus showed reduced body, testes, epididymides, uterus, and ovary weight; antral follicles and corpora lutea were absent and vaginae remained closed. Animals moulted to winter pelage, and low concentrations of each of leptin, testosterone, and prolactin were present in male serum. Phodopus campbelli juveniles also responded to the short photoperiod as measured by reduced body, testes, epididymides, and ovary weight. The summer pelage persisted. However, both sexes of P. campbelli developed functional reproduction under 10 h light:14 h darkness. All females had a patent vagina by 10 weeks; ovaries contained antral follicles and corpora lutea, and uteri were not reduced in weight. In males, the concentrations of testosterone, leptin, and prolactin were not reduced by short photoperiod. Developmental patterns in the three species of hamster, therefore, differ and are not predicted by relatedness or latitude of origin. Other ecological traits, such as predictability of summer rainfall, ambient temperature, and differential responses to social cues might be important.


Silkworm model of biofilm formation: In vivo evaluation of antimicrobial tolerance of a cross-kingdom dual-species (Escherichia coli and Candida albicans) biofilm on catheter material.
Biofilms are formed by microorganisms and their products on the surface of materials such as medical devices. Biofilm formation protects microorganisms from antimicrobial agents. Bacteria and fungi often form dual-species biofilms on the surfaces of medical devices in clinical settings. An experimental system to evaluate in vivo biofilm formation by the pathogenic fungus Candida albicans was established using silkworms inserted with polyurethane fiber (PF), a catheter material. In the present study, we established an in vivo experimental system using silkworms to evaluate the antimicrobial tolerance of Escherichia coli in single- and dual-species biofilms formed on the surface of the PF. The injection of E. coli into the PF-inserted silkworms led to the formation of a biofilm by E. coli on the surface of the PF. E. coli in the biofilm exhibited tolerance to meropenem (MEPM). Furthermore, when E. coli and C. albicans were co-inoculated into the PF-inserted silkworms, a dual-species biofilm formed on the surface of the PF. E. coli in the dual-species biofilm with C. albicans was more tolerant to MEPM than E. coli in the single-species biofilm. These findings suggest the usefulness of an in vivo experimental system using PF-inserted silkworms to investigate the mechanisms of MEPM tolerance in E. coli in single- and dual-species biofilms.


Study of differential proteins in lung adenocarcinoma using laser capture microdissection combined with liquid chip-mass spectrometry technology.
In recent years the proportion of lung adenocarcinoma (adCA) which occurs in lung cancer patients has increased. Using laser capture microdissection (LCM) combined with liquid chip-mass spectrometry technology, we aimed to screen lung cancer biomarkers by studying the proteins in the tissues of adCA. We used LCM and magnetic bead based weak cation exchange (MB-WCX) to separate and purify the homogeneous adCA cells and normal cells from six cases of fresh adCA and matched normal lung tissues. The proteins were analyzed and identified by matrix assisted laser desorption/ionization time-of-fight mass spectrometry (MALDI-OF-MS). We screened for the best pattern using a radial basic function neural network algorithm. About 2.895 × 10(6) and 1.584 × 10(6) cells were satisfactorily obtained by LCM from six cases of fresh lung adCA and matched normal lung tissues, respectively. The homogeneities of cell population were estimated to be over 95% as determined by microscopic visualization. Comparing the differentially expressed proteins between the lung adCA and the matched normal lung group, 221 and 239 protein peaks, respectively, were found in the mass-to-charge ration (M/Z) between 800 Da and 10 000 Da. According to t test, the expression of two protein peaks at 7521.5 M/Z and 5079.3 M/Z had the largest difference between tissues. They were more weakly expressed in the lung adCA compared to the matched normal group. The two protein peaks could accurately separate the lung adCA from the matched normal lung group by the sample distribution chart. A discriminatory pattern which can separate the lung adCA from the matched normal lung tissue consisting of three proteins at 3358.1 M/Z, 5079.3 M/Z and 7521.5 M/Z was established by a radial basic function neural network algorithm with a sensitivity of 100% and a specificity of 100%. Differential proteins in lung adCA were screened using LCM combined with liquid chip-mass spectrometry technology, and a biomarker model was established. It is possible that this technology is going to become a powerful tool in screening and early diagnosis of lung adCA.


Localization and enumeration of T and B lymphocytes in the reproductive tract of laying hens.
Distribution and the relative frequencies of subclasses of T and B lymphocytes in the 360-d-old, healthy laying hens were studied. Avidin-Biotin-Peroxidase Complex (ABC) method was used to detect T cells, whereas Indirect Immunofluorescent Technique (IFT) was applied to detect B cells. Both T and B cells were scattered throughout the ovaries and oviducts. Small lymphoid nodules were found in the upper regions of the oviducts. More T lymphocytes were found in the vagina, ovary, and infundibulum than in the other portions examined, whereas B lymphocytes were mainly found in magnum, uterus, and isthmus. The IgG-containing (B) cells were not found in the ovary. The CD8+ cells were found more close to the lining epithelium or in between epithelial cells, whereas CD4+ cells were found mainly in the lamina propria. The behavior of these cells in certain infectious diseases in which the ovaries and oviducts are major predilection sites would be very important in assessing or determining local immune responses.


Fluids in Random Media and Dimensional Augmentation.
We propose a solution to the puzzle of dimensional reduction in the random field Ising model, asking the following: To what random problem in D=d+2 dimensions does a pure system in d dimensions correspond? For a continuum binary fluid and an Ising lattice gas, we prove that the mean density and other observables equal those of a similar model in D dimensions, but with infinite range interactions and correlated disorder in the extra two dimensions. There is no conflict with rigorous results that the finite range model orders in D=3. Our arguments avoid the use of replicas and perturbative field theory, being based on convergent cluster expansions, which, for the lattice gas, may be extended to the critical point by the Lee-Yang theorem. Although our results may be derived using supersymmetry, they follow more directly from the matrix-tree theorem.


[Primary carcinoma of the female urethra: report of five cases].
Between 1988 and 1996, we treated five patients with primary carcinoma of the female urethra between 65 and 79 years of age. Presenting symptoms included a urethral mass in 2 patients, hematuria in 1, dysuria in 1 and urethral bleeding in 1. Histopathology revealed squamous cell carcinoma in 4 cases and transitional cell carcinoma in 1. Clinical stage according to Grabstald's classification comprised Stage A in two cases, Stages B, C and D in one each. The modes of treatment were surgical resection alone in two, radiation therapy alone in two, and surgery with adjuvant chemotherapy in one case. Three patients without disease and two with disease are olive from 5 to 87 months after diagnosis.


Quantum Dynamics Study of the Potential Energy Minima Effect on Energy Efficiency for the F- + CH3Cl → FCH3 + Cl- Reaction.
The Polanyi rules on the energy efficiency on reactivity are summarized solely from the locations of barriers on the potential energy surfaces. Here, our quantum dynamics study for the F- + CH3Cl → FCH3 + Cl- reaction shows that the two potential energy minima in the entrance channel on the potential energy surface play an essential role in energy efficiency on reactivity. The reactivity of this reaction is dominated by the low collision energies where two distinctive reaction mechanisms involve the two minima in the entrance channel. Overall, the Cl-CH3 stretching motion and C-H3 umbrella motion both are more efficient than the translational motion in promoting this reaction. Although this reaction has a negative energy barrier, our study shows that it is the minima in the entrance channel, together with the energy barrier relative to these minima, that determine the energy efficacy on reactivity.


Oligonucleotide conjugates for therapeutic applications.
Insufficient pharmacokinetic properties and poor cellular uptake are the main hurdles for successful therapeutic development of oligonucleotide agents. The covalent attachment of various ligands designed to influence the biodistribution and cellular uptake or for targeting specific tissues is an attractive possibility to advance therapeutic applications and to expand development options. In contrast to advanced formulations, which often consist of multiple reagents and are sensitive to a variety of preparation conditions, oligonucleotide conjugates are defined molecules, enabling structure-based analytics and quality control techniques. This review gives an overview of current developments of oligonucleotide conjugates for therapeutic applications. Attached ligands comprise peptides, proteins, carbohydrates, aptamers and small molecules, including cholesterol, tocopherol and folic acid. Important linkage types and conjugation methods are summarized. The distinct ligands directly influence biochemical parameters, uptake mechanisms and pharmacokinetic properties.


Predictors of early aortic neck dilatation after endovascular aneurysm repair with EndoAnchors.
Dilatation of the aorta within the proximal neck after endovascular aneurysm repair (EVAR) can be associated with late endoleaks and migration. This study was designed to identify predictors of early neck dilation in patients undergoing EVAR with Heli-FX EndoAnchors (Medtronic, Santa Rosa, Calif) measured perioperatively to 1 year at different longitudinal levels of neck length. The study group of Aneurysm Treatment Using the Heli-FX Aortic Securement System (ANCHOR) comprises 257 consecutive patients prospectively enrolled between April 2012 and September 2014 undergoing EVAR with Heli-FX EndoAnchor implantation at 38 investigational sites. Only patients undergoing EndoAnchor implantation at the time of the initial EVAR were included (primary treatment arm). Aortic diameter was measured at the suprarenal level and at three levels within the proximal neck. Neck dilatation was assessed in 209 patients with adequate computed tomography imaging at baseline and 1 month and in 62 patients at 1 month and 1 year (mean, 11.9 ± 4.0 months). Multivariable analyses were performed to identify independent predictors of perioperative (baseline to 1 month) and early postoperative (1 month to 1 year) aortic dilation at each level; analyses included 6 candidate variables, 6 clinical, and 14 anatomic run in eight models (one at each of the four aortic levels for both time frames). The mean aortic neck dilation at 1 month was 0.2 ± 1.7 mm, 0.7 ± 2.2 mm, and 0.9 ± 3.6 mm at 0 mm, 5 mm, and 10 mm below the lowest renal artery, and 0.0 ± 1.5 mm at the suprarenal level. From 1 month to 1 year, neck dilatation was 0.5 ± 1.6 mm, 0.4 ± 1.5 mm, 0.2 ± 1.8 mm, and -0.3 ± 1.1 mm at the same four levels, respectively. Dilatation of ≥3 mm at level 5 mm distal to the lowest renal artery was observed in 26 patients (12.5%) from preoperative to 1 month and in 5 patients (8.1%) between 1 month and 1 year. Multivariable regression identified several variables predictive of perioperative (preoperative to 1 month) neck dilatation: baseline neck diameter, mural calcium (protective), and endografts with a suprarenal stent. Neck dilatation between 1 month and 1 year was associated with baseline neck diameter, neck length (protective), neck angulation, device oversizing, number of EndoAnchors implanted (protective), and endografts with a suprarenal stent. Aortic diameter and graft oversizing appear to be independent risk factors for early aortic neck dilatation. EndoAnchors have a protective effect on neck dilatation at their usual level of deployment.


The in vivo dynamic interplay of MDC1 and 53BP1 at DNA damage-induced nuclear foci.
MDC1 (NFBD1) and 53BP1 are critical mediators of the mammalian DNA damage response (DDR) at nuclear foci. Here we show by quantitative imaging assays that MDC1 and 53BP1 are similar in total copy number (~1200 copies per focus), but differ substantially in dynamics at both replication-associated nuclear bodies in normal cells and DNA repair foci in ionizing radiation (IR)-damaged cells. The majority of MDC1 (~80%) is extremely mobile and under continuous exchange, with only a small fraction (~20%) remaining immobile at foci irrespective of IR treatment. By contrast, 53BP1 has a smaller mobile fraction (~35%) and a larger immobile fraction (~65%) at nuclear bodies, and becomes more dynamic (~20% increase in mobile pool) upon IR-induced DNA damage. More specifically, the dynamics of 53BP1 is dependent on a minimal foci-targeting region (1231-1709), and differentially regulated by its N-terminus (1-1231) and C-terminal tBRCT domain (1709-1972). Furthermore, MDC1 knockdown, or disruption of 53BP1-MDC1 interaction, reduced the number of 53BP1 molecules at foci by ~60%, but only modestly affected 53BP1 retention. This novel in vivo evidence reveals distinct dynamics of MDC1 and 53BP1 at different types of nuclear structures, and shows that MDC1 directly recruits and retains a subset of 53BP1 for DNA repair.


Microbial modulation of plant ethylene signaling: ecological and evolutionary consequences.
The plant hormone ethylene is one of the central regulators of plant development and stress resistance. Optimal ethylene signaling is essential for plant fitness and is under strong selection pressure. Plants upregulate ethylene production in response to stress, and this hormone triggers defense mechanisms. Due to the pleiotropic effects of ethylene, adjusting stress responses to maximize resistance, while minimizing costs, is a central determinant of plant fitness. Ethylene signaling is influenced by the plant-associated microbiome. We therefore argue that the regulation, physiology, and evolution of the ethylene signaling can best be viewed as the interactive result of plant genotype and associated microbiota. In this article, we summarize the current knowledge on ethylene signaling and recapitulate the multiple ways microorganisms interfere with it. We present ethylene signaling as a model system for holobiont-level evolution of plant phenotype: this cascade is tractable, extremely well studied from both a plant and a microbial perspective, and regulates fundamental components of plant life history. We finally discuss the potential impacts of ethylene modulation microorganisms on plant ecology and evolution. We assert that ethylene signaling cannot be fully appreciated without considering microbiota as integral regulatory actors, and we more generally suggest that plant ecophysiology and evolution can only be fully understood in the light of plant-microbiome interactions.


Electronic structures of ruthenium and osmium complexes of 9,10-phenanthrenequinone.
The reaction of 9,10-phenanthrenequinone (PQ) with [M(II)(H)(CO)(X)(PPh(3))(3)] in boiling toluene leads to the homolytic cleavage of the M(II)-H bond, affording the paramagnetic trans-[M(PQ)(PPh(3))(2)(CO)X] (M = Ru, X = Cl, 1; M = Os, X = Br, 3) and cis-[M(PQ)(PPh(3))(2)(CO)X] (M = Ru, X = Cl, 2; M = Os, X = Br, 4) complexes. Single-crystal X-ray structure determinations of 1, 2·toluene, and 4·CH(2)Cl(2), EPR spectra, and density functional theory (DFT) calculations have substantiated that 1-4 are 9,10-phenanthrenesemiquinone radical (PQ(•-)) complexes of ruthenium(II) and osmium(II) and are defined as trans-[Ru(II)(PQ(•-))(PPh(3))(2)(CO)Cl] (1), cis-[Ru(II)(PQ(•-))(PPh(3))(2)(CO)Cl] (2), trans-[Os(II)(PQ(•-))(PPh(3))(2)(CO) Br] (3), and cis-[Os(II)(PQ(•-))(PPh(3))(2)(CO)Br] (4). Two comparatively longer C-O [average lengths: 1, 1.291(3) Å; 2·toluene, 1.281(5) Å; 4·CH(2)Cl(2), 1.300(8) Å] and shorter C-C lengths [1, 1.418(5) Å; 2·toluene, 1.439(6) Å; 4·CH(2)Cl(2), 1.434(9) Å] of the OO chelates are consistent with the presence of a reduced PQ(•-) ligand in 1-4. A minor contribution of the alternate resonance form, trans- or cis-[M(I)(PQ)(PPh(3))(2)(CO)X], of 1-4 has been predicted by the anisotropic X- and Q-band electron paramagnetic resonance spectra of the frozen glasses of the complexes at 25 K and unrestricted DFT calculations on 1, trans-[Ru(PQ)(PMe(3))(2)(CO)Cl] (5), cis-[Ru(PQ)(PMe(3))(2)(CO)Cl] (6), and cis-[Os(PQ)(PMe(3))(2)(CO)Br] (7). However, no thermodynamic equilibria between [M(II)(PQ(•-))(PPh(3))(2)(CO)X] and [M(I)(PQ)(PPh(3))(2)(CO)X] tautomers have been detected. 1-4 undergo one-electron oxidation at -0.06, -0.05, 0.03, and -0.03 V versus a ferrocenium/ferrocene, Fc(+)/Fc, couple because of the formation of PQ complexes as trans-[Ru(II)(PQ)(PPh(3))(2)(CO)Cl](+) (1(+)), cis-[Ru(II)(PQ)(PPh(3))(2)(CO)Cl](+) (2(+)), trans-[Os(II)(PQ)(PPh(3))(2)(CO)Br](+) (3(+)), and cis-[Os(II)(PQ)(PPh(3))(2)(CO)Br](+) (4(+)). The trans isomers 1 and 3 also undergo one-electron reduction at -1.11 and -0.96 V, forming PQ(2-) complexes trans-[Ru(II)(PQ(2-))(PPh(3))(2)(CO)Cl](-) (1(-)) and trans-[Os(II)(PQ(2-))(PPh(3))(2)(CO)Br](-) (3(-)). Oxidation of 1 by I(2) affords diamagnetic 1(+)I(3)(-) in low yields. Bond parameters of 1(+)I(3)(-) [C-O, 1.256(3) and 1.258(3) Å; C-C, 1.482(3) Å] are consistent with ligand oxidation, yielding a coordinated PQ ligand. Origins of UV-vis/near-IR absorption features of 1-4 and the electrogenerated species have been investigated by spectroelectrochemical measurements and time-dependent DFT calculations on 5, 6, 5(+), and 5(-).


Changes in plasma calcium during septic shock.
Previous studies have documented a decrease in plasma calcium occurring early after trauma, haemorrhage and cardiac arrest. Therefore, changes in plasma calcium in an ovine experimental model of septic shock due to intraperitoneal sepsis were investigated. Subjects were volume-loaded with Ringer's lactate solution. Plasma calcium and albumin were measured before and 24 h after surgical induction of sepsis. Subjects were divided into two groups according to the severity of shock. Group 1 (n = 8) developed severe hyperdynamic sepsis with renal failure. Group 2 (n = 8) showed no change in blood pressure, cardiac output or renal function. Plasma calcium fell significantly in both groups, and was lower in Group 1 during sepsis (Group 1: 2.36 +/- 0.19 to 1.84 +/- 0.14 mmol l-1; Group 2: 2.34 +/- 0.12 to 2.01 +/- 0.13 mmol l-1; mean +/- SD; both P < 0.001). Plasma albumin fell during sepsis, and the reduction was greater in Group 1. The plasma calcium, corrected for albumin, was still significantly reduced and was similar in each group during sepsis (Group 1: 2.55 +/- 0.13 to 2.23 +/- 0.12 mmol l-1; Group 2: 2.50 +/- 0.08 to 2.27 +/- 0.09 mmol l-1; both P < 0.001). In this large animal model of septic shock, which reproduces the important features of clinical sepsis, there were significant decrements in uncorrected and corrected plasma calcium 24 h after the surgical induction of intraperitoneal sepsis. These changes may contribute to the pathophysiology of this condition.